Diseases caused by influenza virus and by respiratory syncytial virus (RSV) remain a medical priority. For this program project grant, we have assembled a multidisciplinary group of scientists to apply the latest technological advances in genomics and virology to shed new light on the cellular response to viral infection. We will concentrate on the specific effects of virally encoded interferon antagonists on the gene expression patterns of the infected cell. We will use novel, genetically engineered viruses (influenza and RSV) which display varying degrees of interferon-sensitivity (or differing capacities to induce interferon) as molecular probes to study the cellular response to infection. We will characterize the different biological results with expression profiles using DNA microarrays (Project 3). The application of bioinformatics (Project 4) will allow the interpretation of the global patterns of gene expression in virus-infected cells such that we can begin to understand the common strategies used by respiratory RNA viruses to evade the innate immune response and suggest mechanisms for virulence. Such analyses may identify new components of the host innate antiviral response, may facilitate the development of new vaccine and/or antiviral approaches and should illuminate new avenues of research related to host-virus interaction.